Selincro · 4.6 Fertility, pregnancy and lactation · 1

HOS-096432 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The frequencies of the adverse reactions in Table 1 were calculated based on three randomised, double-blind, placebo-controlled studies in patients with alcohol dependence. The most common adverse reactions were nausea, dizziness, insomnia, and headache. The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration. Confusional state and, rarely, hallucinations and dissociation were reported in the clinical studies. The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration (a few hours to a few days). Most of these adverse reactions resolved during continued treatment and did not recur upon repeated administration. While these events were generally short- lasting, they could represent alcoholic psychosis, alcohol withdrawal syndrome, or comorbid psychiatric disease. Tabulated list of adverse reactions Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), or not known (cannot be estimated from the available data). 6 Table 1. Frequencies of adverse reactions System Organ Class Frequency Adverse Reaction Metabolism and nutrition disorders Common Decreased appetite Very common Insomnia Common Sleep disorder Confusional state Restlessness Libido decreased (including loss of Psychiatric disorders libido) Uncommon Hallucination (including hallucination auditory, hallucination tactile, hallucination visual, and somatic hallucination) Dissociation Very Common Dizziness

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HOS-096428 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients taking opioid agonists (such as opioid analgesics, opioids for substitution therapy with opioid agonists (e.g. methadone) or partial agonists (e.g. buprenorphine)) (see section 4.4). Patients with current or recent opioid addiction. Patients with acute symptoms of opioid withdrawal. Patients for whom recent use of opioids is suspected. Patients with severe hepatic impairment (Child-Pugh classification). Patients with severe renal impairment (eGFR <30 ml/min per 1.73 m2). Patients with a recent history of acute alcohol withdrawal syndrome (including hallucinations, seizures, and delirium tremens).

HOS-096427 · has-indication-information · PDF-Seite 2

Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (DRL) [see section 5.1], without physical withdrawal symptoms and who do not require immediate detoxification. Selincro should only be prescribed in conjunction with continuous psychosocial support focused on treatment adherence and reducing alcohol consumption. Selincro should be initiated only in patients who continue to have a high DRL two weeks after initial assessment.

HOS-096430 · has-interaction-information · PDF-Seite 5

No in vivo drug-drug interaction studies have been conducted. Based on in vitro studies, no clinically relevant interactions between nalmefene, or its metabolites, and concomitantly administered medicinal products metabolised by the most common CYP450 and UGT enzymes or membrane transporters are anticipated. Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme (for example, diclofenac, fluconazole, medroxyprogesterone acetate, meclofenamic acid) may significantly increase the exposure to nalmefene. This is unlikely to present a problem with occasional use, but if long-term concurrent treatment with a potent UGT2B7 inhibitor is initiated, a potential for an increase in nalmefene exposure cannot be excluded (see section 4.4). Conversely, concomitant administration with a UGT inducer (for example, dexamethasone, phenobarbital, rifampicin, omeprazole) may potentially lead to subtherapeutic nalmefene plasma concentrations. If Selincro is taken concomitantly with opioid agonists (for example, certain types of cough and cold medicinal products, certain antidiarrhoeal medicinal products, and opioid analgesics), the patient may not benefit from the opioid agonist. There is no clinically relevant pharmacokinetic drug-drug interaction between nalmefene and alcohol. There seems to be a small impairment in cognitive and psychomotor performance after administration of nalmefene. However, the effect of nalmefene and alcohol in combination did not exceed the sum of the effects of each substance when taken alone. Simultaneous intake of alcohol and Selincro does not prevent the intoxicating effects of alcohol.

HOS-096431 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited data (fewer than 300 pregnancy outcomes) from the use of nalmefene in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). Selincro is not recommended during pregnancy. Breast-feeding Available pharmacodynamic/toxicological data in animals have shown excretion of nalmefene/metabolites in milk (see section 5.3). It is unknown whether nalmefene is excreted in human milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Selincro therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman. 5 Fertility In fertility studies in rats, no effects were observed for nalmefene on fertility, mating, pregnancy, or sperm parameters.

HOS-096429 · has-warning-information · PDF-Seite 3

Selincro is not for patients for whom the treatment goal is immediate abstinence. Reduction of alcohol consumption is an intermediate goal on the way to abstinence. 3 Opioid administration In an emergency situation when opioids must be administered to a patient taking Selincro, the amount of opioid required to obtain the desired effect may be greater than usual. The patient should be closely monitored for symptoms of respiratory depression as a result of the opioid administration and for other adverse reactions. If opioids are needed in an emergency, the dose must always be titrated individually. If unusually large doses are required, close observation is necessary. Selincro should be temporarily discontinued for 1 week prior to the anticipated use of opioids, for example, if opioid analgesics might be used during elective surgery. The prescriber should advise patients that it is important to inform their health care professional of last Selincro intake if opioid use becomes necessary. Caution should be exercised when using medicinal products containing opioids (for example, cough medicines, opioid analgesics (see section 4.5)). Comorbidity Psychiatric disorders Psychiatric effects were reported in clinical studies (see section 4.8). If patients develop psychiatric symptoms that are not associated with treatment initiation with Selincro, and/or that are not transient, the prescriber should consider alternative causes of the symptoms and assess the need for continuing treatment with Selincro. Selincro has not been investigated in patients with unstable psychiatric disease. Caution should be exercised if Selincro is prescribed to patients with current psychiatric comorbidity such as major depressive disorder. The increased suicidal risk in alcohol and substances abusers, with or without accompanying depression, is not reduced by the intake of nalmefene. Seizure disorders There is limited experience in patients with a history of seizure disorders, including alcohol withdrawal seizures. Caution is advised if treatment aimed at reduction of alcohol consumption is started in such patients. Renal or hepatic impairment Selincro is extensively metabolised by the liver and excreted predominantly in the urine. Therefore, caution should be exercised when prescribing Selincro to patients with mild or moderate hepatic or mild or moderate renal impairment, for example, by more frequent monitoring. Caution

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